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Cholinergic inhibition of follicle-stimulating hormone-induced progestin production by cultured rat granulosa cells
Journal article   Open access   Peer reviewed

Cholinergic inhibition of follicle-stimulating hormone-induced progestin production by cultured rat granulosa cells

B. G Kasson and A. J. W Hsueh
Biology of reproduction, Vol.33(5), pp.1158-1167
1985
DOI: 10.1095/biolreprod33.5.1158
PMID: 3000464
url
https://doi.org/10.1095/biolreprod33.5.1158View
Published (Version of record) Open Access

Abstract

The influence of cholinomimetics on follicle-stimulating hormone (FSH)-induced progestin production was studied in a primary culture of rat granulosa cells. Cells were cultured for 2 days with FSH and Δ4-androstenedione in the presence or absence of increasing concentrations of cholinergic agonists. Although ineffective as stimulators of steroidogenesis by themselves, the three nicotinic receptor-selective agonists lobeline, dimethylphenylpiperazinium iodide (DMPP), and phenyltrimethylammonium iodide (PTMA) inhibited FSH-induced progesterone and 20α-hydroxy-pregn-4-en-3-one production in dose-dependent fashions. The rank order of inhibitory potencies was lobeline > DMPP > PTMA with IC50 values of 2 x 10-6 M, 3 x 10-5 M, and 3 x 10-4 M, respectively. In contrast, the muscarinic receptor-selective agonists muscarine and bethanechol failed to inhibit steroid production. The inhibitory effect of lobeline on the time course of FSH-induced steroid production indicated an immediate inhibitory action; however, this inhibition was readily reversed upon removal of the drug. Further studies demonstrated that the FSH-stimulated increase in intracellular cAMP levels, as well as progesterone production induced by cholera toxin and forskolin (agents that stimulate cAMP production) and by dibutyryl cAMP (a cAMP analog), were also suppressed by lobeline. The present observations indicate that nicotinic, but not muscarinic, cholinergic agonists inhibit progesterone biosynthesis in cultured granulosa cells and suggest that endogenous acetylcholine may play a modulatory role in ovarian steroidogenesis.
Biological and medical sciences Fundamental and applied biological sciences. Psychology Hormone metabolism and regulation Mammalian female genital system Vertebrates: reproduction

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